The long-term goal of this research is to understand in molecular detail how cells choose to form a particular organ and how they carry out this decision. The Principal Investigator proposes to address these questions by a systematic analysis of formation of a simple tissue, the salivary glands, in a genetically-tractable organism, the fruit fly, Drosophila melanogaster. In the past several years, the Principal Investigator has identified the factors that control where salivary glands will form and the number of cells committed to a salivary gland fate. In the next few years, the proposed studies will provide information on how these factors work in combination to control expression of salivary gland genes. The Principal Investigator also has perhaps the largest single collection of genes expressed in a specific tissue. Her goal is to pinpoint and characterize the genes that function very early in salivary gland development, particularly genes that coordinate the major morphogenetic movements required to internalize the salivary glands and to form functional epithelial tubes. To achieve these goals, four specific aims are proposed. In Aim 1, studies are proposed to test if activation of three early salivary gland genes by the transcription factors SCR, EXD and HTH is direct and, if so, will learn how TSH, ABD-B and DPP-signaling block activation. In Aim 2, studies are proposed to address the role of two early transcription factors, FKH and HKB, in salivary gland internalization. Fkh mutants fail to complete internalization of the salivary gland and show extensive salivary cell death. Hkb mutants initiate internalization at the wrong place and form abnormally shaped salivary glands. In Aim 3, studies are proposed to address the role of two genes, rib and D-SemaII, in positioning the salivary gland. Rib mutants have defects in directed migration of salivary gland cells and in D-SemaII mutants the distal portion of the salivary gland is abnormally positioned. In Aim 4, studies are proposed to find new genes required for salivary gland morphogenesis. These new genes will be identified both from the Principal Investigator's collection of genes known to be expressed in the developing salivary gland and from an EMS saturation screen. The proposed studies will provide a working blueprint for the early events of organ formation in all higher organisms.